Spatial Proteomics Profiles of Aldosterone-producing Adenoma and Unilateral Hyperplasia

Sponsor

Third Military Medical University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05927961

Collaborator

(none)

Enrollment

Location

9.8

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary aldosteronism (PA) is a common cause of secondary hypertension, which is characterized by excessive aldosterone production by the adrenal gland. Excessive aldosterone can significantly increase the risk of cardiovascular disease and stroke. Patients with aldosterone-producing adenoma (APA) or unilateral hyperplasia (UAH) can be cured by unilateral adrenalectomy. The adrenal cortex is the outer part of the adrenal gland and is subdivided into three layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis. And the outermost layer is the zona glomerulosa, and it's full of cells that make the hormone aldosterone. Although it has been investigated that the main cause of APA or UAH is the mutations of different calcium ion channels, including KCNJ5, CACNA1D, CLCN2 et al, it is still unknown whether there are any other changes of other proteins in different layers. Therefore, the investigators designed the study to characterize the proteomics profiles of adrenal adenoma/hyperplasia leading to primary aldosterone and identify biomarkers for early identification of PA by using spatial proteomics. The samples from adrenal adenoma or hyperplasia will be collected and analyzed by spatial proteomics in Hangzhou Jingjie Biotechnology Co., Ltd. The differentially expressed proteins in different layers will be screened out between APA and UAH, APA and its adjacent normal tissues, and UAH and its adjacent normal tissues, respectively. And KEGG analysis will be conducted to determine enriched pathway in these differentially expressed protein, respectively.

Condition or Disease	Intervention/Treatment	Phase
Primary Aldosteronism Due to Aldosterone Producing Adenoma Primary Aldosteronism Due to Adrenal Hyperplasia (Bilateral)	Diagnostic Test: histopathology

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Spatial Proteomics Profiles of Adrenal Adenoma/Hyperplasia Leading to Primary Aldosterone

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

May 25, 2024

Arms and Interventions

Arm	Intervention/Treatment
aldosterone-producing adenoma Histopathology shows a clear boundary between adrenal adenoma and surrounding normal tissue.	Diagnostic Test: histopathology There is a clear boundary between adrenal adenoma and surrounding normal tissue. There is no clear boundary between adrenal hyperplasia and surrounding normal tissues.
unilateral hyperplasia Histopathology shows no clear boundary between adrenal hyperplasia and surrounding normal tissues.	Diagnostic Test: histopathology There is a clear boundary between adrenal adenoma and surrounding normal tissue. There is no clear boundary between adrenal hyperplasia and surrounding normal tissues.

Arm

Intervention/Treatment

aldosterone-producing adenoma

Histopathology shows a clear boundary between adrenal adenoma and surrounding normal tissue.

Diagnostic Test: histopathology

There is a clear boundary between adrenal adenoma and surrounding normal tissue. There is no clear boundary between adrenal hyperplasia and surrounding normal tissues.

unilateral hyperplasia

Histopathology shows no clear boundary between adrenal hyperplasia and surrounding normal tissues.

Diagnostic Test: histopathology

There is a clear boundary between adrenal adenoma and surrounding normal tissue. There is no clear boundary between adrenal hyperplasia and surrounding normal tissues.

Outcome Measures

Primary Outcome Measures

Screening for the biomarkers. [After APA/UAH resection/biopsy, usually within 6 months]
Histological validation of the CYP11B2 positive area in APA and UAH by immunohistochemical staining (IHC). Some specimens will be characterized more deeply with advanced spatial proteomics technologies to identify the biomarkers.

Secondary Outcome Measures

Incorporate biomarkers into the accurate and early diagnosis of PA. [12 months]
Verifying the relationship between biomarkers and clinical presentations, including plasma aldosterone concentrations (PAC), aldosterone to rein ratio (ARR), direct renin concentration (DRC), and serum potassium, etc. Comparing the relationships between biomarkers and risk factors, including osas and family history, etc. Establishing a mathematical model for diagnosing PA through machine learning and studying the pathogenesis of PA through corresponding animal models.
Identifying the relationship between biomarkers and the prognosis of PA. [12 months]
The alteration of blood pressure and medication status are investigated through 3 months followed up. Verifying the relationship between the biomarkers and the function of APA and UAH, as well as the prognosis of PA.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

According to the 2020 guidelines for primary aldosteronism, patients with positive primary aldosteronism confirmed test;
Patients with predominant unilateral aldosterone secretion at AVS; adrenal CT suggesting unilateral adrenal adenoma (> 0.8cm diameter) and no abnormalities in contralateral adrenal morphology.
Patients who agreed to do the adrenalectomy.

Exclusion Criteria:

adrenal CT suggests abnormal bilateral adrenal morphology or unilateral nodules.
glucocorticoids can treat aldosteronism (GRA) and familial aldosteronism.
other secondary hypertension: renal parenchymal hypertension, renal artery stenosis, Cushing syndrome, adrenal myeloid hyperplasia, aortic narrowing, obstructive sleep apnea hypoventilation syndrome.
any other unsuitable condition for surgery.
Patients who refused to perform adrenalectomy.